Oligonol Ameliorates CCl₄-Induced Liver Injury in Rats via the NF-Kappa B and MAPK Signaling Pathways.

Abstract

Oxidative stress is thought to be a key risk factor in the development of hepatic diseases. Blocking or retarding the reactions of oxidation and the inflammatory process by antioxidants could be a promising therapeutic intervention for prevention or treatment of liver injuries. Oligonol is a low molecular weight polyphenol containing catechin-type monomers and oligomers derived from lychee fruit. In this study, we investigated the anti-inflammatory effect of oligonol on carbon tetrachloride- (CCl4-) induced acute hepatic injury in rats. Oral administration of oligonol (10 or 50 mg/kg) reduced CCl4-induced abnormalities in liver histology and serum AST and serum ALT levels. Oligonol treatment attenuated the CCl4-induced production of inflammatory mediators, including TNF-α, IL-1β, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) mRNA levels. Western blot analysis showed that oligonol suppressed proinflammatory nuclear factor-kappa B (NF-κB) p65 activation, phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinases (MAPKs) as well as Akt. Oligonol exhibited strong antioxidative activity in vitro and in vivo, and hepatoprotective activity against t-butyl hydroperoxide-induced HepG2 cells. Taken together, oligonol showed antioxidative and anti-inflammatory effects in CCl4-intoxicated rats by inhibiting oxidative stress and NF-κB activation via blockade of the activation of upstream kinases including MAPKs and Akt.

• Authors: Jeonghyeon Bak, Nam Kyung Je, Hae Young Chung, Takako Yokozawa, Sik Yoon, Jeon-Ok Moon
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2016 Pg. 3935841 ( 2016) ISSN: 1942-0994 [Electronic] United States
• PMID: 26798422 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Biphenyl Compounds
• Ferrous Compounds
• Interleukin-1beta
• NF-kappa B
• Phenols
• Picrates
• Tumor Necrosis Factor-alpha
• oligonol
• ferrous sulfate
• Malondialdehyde
• Catechin
• tert-Butylhydroperoxide
• Hydrogen Peroxide
• Carbon Tetrachloride
• 1,1-diphenyl-2-picrylhydrazyl
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• PTGS2 protein, human
• Aspartate Aminotransferases
• Alanine Transaminase
• Proto-Oncogene Proteins c-akt

Topics

• Alanine Transaminase (blood)
• Animals
• Antioxidants (pharmacology, therapeutic use)
• Aspartate Aminotransferases (blood)
• Biphenyl Compounds (chemistry)
• Carbon Tetrachloride
• Catechin (analogs & derivatives, pharmacology, therapeutic use)
• Cell Nucleus (drug effects, metabolism)
• Cyclooxygenase 2 (metabolism)
• Enzyme Activation (drug effects)
• Ferrous Compounds (toxicity)
• Gene Expression Regulation (drug effects)
• Hep G2 Cells
• Humans
• Hydrogen Peroxide (toxicity)
• Interleukin-1beta (genetics, metabolism)
• Lipid Peroxidation (drug effects)
• Liver (drug effects, pathology)
• Liver Diseases (blood, drug therapy, enzymology, genetics)
• MAP Kinase Signaling System (drug effects)
• Malondialdehyde (metabolism)
• NF-kappa B (metabolism)
• Nitric Oxide Synthase Type II (genetics, metabolism)
• Phenols (pharmacology, therapeutic use)
• Picrates (chemistry)
• Protein Transport (drug effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats, Sprague-Dawley
• Tumor Necrosis Factor-alpha (genetics, metabolism)
• tert-Butylhydroperoxide